Antonio José V. Carneiro

Prevalence of periodontitis and DMFT index in patients with Crohn's disease and ulcerative colitis

AIM To compare the prevalence of periodontal disease and the decayed, missing and filled teeth (DMFT) index in patients with Crohns disease (CD) and ulcerative colitis (UC) with those without these diseases. MATERIAL AND METHODS Ninety-nine CD (39.0 SD+/-12.9 years), 80 UC (43.3 SD+/-13.2) and 74 healthy controls (40.3 SD+/-12.9) were compared for DMFT index and presence of periodontitis. Probing pocket depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), plaque and DMFT index were measured on all subjects. The presence of periodontitis was defined as having CAL > or =3 mm in at least four sites in different teeth. RESULTS Significantly more patients with UC (90.0%; p<0.001) and CD (81.8%; p=0.03) had periodontitis than controls (67.6%). Among smokers, UC patients had significantly more periodontitis. CD had a greater mean DMFT score (18.7 versus 13.9; p=0.031) compared with controls and UC had greater median PPD (2.2 versus 1.7 mm; p<0.0001) than controls. Among non-smokers, CD (2.4 mm; p<0.0001) and UC showed deeper pockets (2.3 mm; p<0.0001) compared with controls (1.5 mm). UC had a greater mean DMFT score (15.3 versus 12.1; p=0.037) compared with controls. CONCLUSIONS CD and UC patients had higher DMFT and prevalence of periodontitis than controls, but smoking was an effect modifier.

Overexpression of ATP-activated P2X7 Receptors in the Intestinal Mucosa Is Implicated in the Pathogenesis of Crohnʼs Disease

Background:Extracellular nucleotides released in conditions of cell stress alert the immune system from tissue injury or inflammation. We hypothesized that the P2X7 receptor (P2X7-R) could regulate key elements in inflammatory bowel disease pathogenesis. Methods:Colonoscopy samples obtained from patients with Crohns disease (CD), ulcerative colitis, and controls were used to analyze P2X7-R expression by RT and real-time PCR, immunohistochemistry, and confocal microscopy. Inflammatory response was determined by the levels of cytokines by enzyme-linked immunosorbent assay in cultures of intestinal explants. Apoptosis was determined by the TUNEL assay. P2X7-R−/− C57BL/6 mice were treated with trinitrobenzene sulfonic acid or dextran sulfate sodium (DSS) for inducing colitis. Results:P2X7-R was expressed in higher levels in inflamed CD epithelium and lamina propria, where it colocalizes more with dendritic cells and macrophages. Basal levels of P2X7-R mRNA were higher in CD inflamed mucosa compared with noninflamed CD and controls and were upregulated after interferon-&ggr; in controls. Apoptotic rates were higher in CD epithelium and lamina propria compared with ulcerative colitis and controls. Levels of tumor necrosis factor-&agr;, interleukin (IL)-1&bgr;, and IL-17 were higher, whereas IL-10 was lower in CD compared with controls. Levels of tumor necrosis factor-&agr;-&agr; and interleukin-1&bgr; increased after adenosine-triphosphate and decreased after KN62 treatment in CD. P2X7-R−/− animals did not develop trinitrobenzene sulfonic acid or DSS colitis. Conclusions:The upregulation of P2X7-R in CD inflamed mucosa is consistent with the involvement of purinoceptors in inflammation and apoptosis. These observations may implicate purinergic signaling in the pathogenesis of intestinal inflammation, and the P2X7-R may represent a novel therapeutic target in CD.

Hedgehog pathway signaling regulates human colon carcinoma HT-29 epithelial cell line apoptosis and cytokine secretion.

The Hedgehog (Hh) pathway is involved in embryogenesis and physiologic processes including cell survival and proliferation. We used the HT-29 and other human colon carcinoma cell lines to investigate Hh signaling and biological functions in colonic epithelial cells. HT-29 cells were cultured under different conditions and exposed to various stimuli. The expression of Hh pathway components and related genes and proteins were assessed by real-time PCR and immunofluorescence. Viability, apoptosis and cell proliferation were measured by the MTT assay, Annexin-V/7-AAD staining and BrdU uptake, respectively. Chemokines production was measured by ELISA in culture supernatants. Indian and Sonic Hh mRNA levels and the downstream transcription factors Gli-1 and Gli-2 increased following treatment with Hh agonists and butyrate, but decreased upon exposure to cyclopamine or GANT61. BMP4 and BMP7 expression increased after stimulation with Hh agonists. Gli-1 protein expression increased after Hh agonists and decreased following cyclopamine. Exposure to Hh agonists promoted β-catenin reduction and subcellular redistribution. Levels of IL-8 and MCP-1 decreased upon exposure to Hh agonists compared to Hh antagonists, LPS, IFN-γ or EGF. Monocyte chemotaxis decreased upon exposure to supernatants of HT-29 cells treated with Shh compared to Hh antagonists, LPS and IFN-γ. Cellular incorporation of BrdU and cell viability decreased following Hh blockade. Hh agonists abrogated the anti-CD95 induced apoptosis. Hh pathway is a key controller of colon cancer cells, as demonstrated by its effect in dampening inflammatory signals and antagonizing apoptosis. The differential expression of Hh components may underlie abnormalities in the local immune response and in epithelial barrier integrity, with potential homeostatic implications for the development of colonic inflammation and malignancies.

Prognostic Significance of p53 Protein Expression in Early Gastric Cancer

Mutations of the p53 tumor suppressor gene have been associated with abnormalities in cell cycle regulation, DNA repair and synthesis, apoptosis, and it has been implicated in the prognosis of advanced gastric cancer. The aim of this study was to evaluate the occurrence of p53 gene mutation and its possible prognostic implications in early gastric cancer. In a retrospective study, we studied 80 patients with early gastric cancer treated surgically between 1982 and 2001. Mutation of p53 gene was investigated in surgical gastric specimens by immunohistochemistry, and results were analyzed in relation to gender, age, macroscopic appearance, size and location of tumor, presence of lymph nodes, Lauren’s histological type, degree of differentiation, and the 5-year survival. The expression of p53 was more frequent among the intestinal type (p = 0.003), the differentiated (p = 0.007), and the macroscopically elevated tumors (p = 0.038). Nevertheless, the isolated expression of p53 was not associated with the 5-year survival, or with the frequency of lymph node involvement. The degree of differentiation was detected as an independent factor related to the outcome of patients (0.044). Significantly shorter survival time was found in p53-negative compared with p53-positive patients, when considering the degree of differentiation of tumors, as assessed by Cox regression analysis (0.049). The association of p53 with the intestinal type, the degree of differentiation and morphological characteristics, may reflect the involvement of chronic inflammatory process underlying early gastric cancer. In this population sample, the expression of p53 alone has no prognostic value for early gastric cancer. However, the significant difference in p53 expression between subgroups of degree of differentiation of tumors can influence post-operative outcome of patients and may be related to possible distinct etiopathogenic subtypes.

Ecological study of gastric cancer in Brazil: Geographic and time trend analysis

AIM To investigate the geographic distributions and time trends of gastric cancer (GC) incidence and mortality in Brazil. METHODS An ecological study of the DATASUS registry was conducted by identifying hospitalizations for GC between January 2005 and December 2010. The data included information on the gender, age, and town of residence at the time of hospital admission and death. RESULTS The GC rates, adjusted according to available hospital beds, decreased from 13.8 per 100000 in 2005 to 12.7 per 100000 in 2010. The GC rates decreased more among the younger age groups, in which the male-to-female difference also decreased in comparison to the older age groups. Although the lethality rates tended to increase with age, young patients were proportionally more affected. The spatial GC distribution showed that the rates were higher in the south and southeast. However, while the rates decreased in the central-west and south, they increased in the northern regions. A geographic analysis showed higher rates of GC in more urbanized areas, with a coast-to-inland gradient. Geographically, GC lethality overlapped greatly with the hospital admission rates. CONCLUSION The results of this study support the hypothesis of a critical role for environmental factors in GC pathogenesis. The declining rates in young patients, particularly males, suggest a relatively recent decrease in the exposure to risk factors associated with GC. The spatial distribution of GC indicates an ongoing dynamic change within the Brazilian environment.

Thiopurine-methyltransferase variants in inflammatory bowel disease: prevalence and toxicity in Brazilian patients.

AIM To analyze the prevalence of thiopurine-methyltransferase (TPMT) genotypes and their association with drug toxicity in inflammatory bowel disease (IBD) patients from southeastern Brazil. METHODS A total of 219 consecutive patients with IBD, of which 146 had Crohns disease and 73 had ulcerative colitis, regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the State University of Rio de Janeiro, a tertiary referral center, were enrolled in this study from February 2009 to January 2011. We analyzed the presence of major TPMT genetic variants (TPMT 2, 3A, 3C) in IBD patients by means of a specific allele and RFLP-PCR. Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/Sodium Dodecyl Sulfate digestion and phenol-chloroform extraction. TPMT 2 (C238G), TPMT 3A (G460A/A719G), and TPMT 3C (A719G) genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers. Clinical data were systematically recorded, and correlated with the genotype results. RESULTS The distribution of the selected TPMT gene polymorphism TPMT 2 (C238G), TPMT 3A (G460A/A719G), and TPMT 3C (A719G) genotypes was 3.6%, 5.4%, and 7.7% of the patients, respectively. Among the side effects recorded from patients taking azathioprine, 14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes, while 6 patients had liver toxicity, and 2 patients exhibited myelosuppression/neutropenia. TPMT polymorphisms were detected in 37/219 patients (8 heterozygous for 2, 11 heterozygous for 3A, and 18 heterozygous for 3C). No homozygotic polymorphisms were found. Despite the prevalence of the TPMT 3C genotype, no differences among the genotype frequencies were significant. Although no association was detected regarding myelotoxicity or hepatotoxicity, a trend towards the elevation of pancreatic enzymes was observed for TPMT 2 and TPMT 3C genotypes. CONCLUSION The prevalence of TPMT genotypes was high among Brazilian patients. Variants genes 2 and 3C may be associated with azathioprine pancreatic toxicity in a IBD southeastern Brazilian population.

The socio-economic impact of work disability due to inflammatory bowel disease in Brazil

BackgroundInflammatory bowel disease (IBD) might have economic and social impacts in Brazil, where its prevalence has increased recently. This study aimed to assess disability due to IBD in the Brazilian population and demographic factors potentially associated with absence from work.MethodsAnalysis was performed using the computerized Single System of Social Security Benefits Information, with a cross-check for aid pension and disability retirement, for Crohn’s disease (CD) and ulcerative colitis (UC). Additional data were obtained from the platform, including the average values, benefit duration, age, gender and region of the country.ResultsTemporary disability occurred more frequently with UC, whereas permanent disability was more frequent with CD. Temporary disability affected more younger patients with CD than patients with UC. Temporary work absences due to UC and CD were greater in the South, and the lowest absence rates due to CD were noted in the North and Northeast. Absence from work was longer (extending for nearly a year) in patients with CD compared to those with UC. The rates of temporary and permanent disability were greater among women. Permanent disability rates were higher in the South (UC) and Southeast (CD). The value of benefits paid for IBD represented approximately 1% of all social security benefits. The benefits paid for CD were higher than for UC, whereas both tended to decrease from 2010 to 2014.ConclusionsIn Brazil, IBD frequently causes disability for prolonged periods and contributes to early retirement. Reduction trends may reflect improvements in access to health care and medication. Vocational rehabilitation programs may positively impact social security and the patients’ quality of life.

Effects of oral nutritional supplementation on the intestinal mucosa of patients with AIDS

Weight loss is a major component of the clinical syndrome in patients with acquired immunodeficiency syndrome (AIDS). The impact of malnutrition on the outcome of the disease has been unappreciated in many investigations. The authors evaluated the effects of oral nutritional supplementation on the morphology and immunology of the intestinal mucosa of patients with AIDS. Twelve patients with AIDS without diarrhea or opportunistic infections, with at least 10% of body weight loss over 1 year, were submitted to anthropometric measures, peripheral blood T-lymphocyte counts, and peroral jejunal biopsy before and after oral nutritional supplementation. An industrialized peptide-based formula containing omega-3 fatty acids was given for 6 weeks. Jejunal samples were analyzed by histomorphometry, including villous-to-crypt ratio, lamina propria, and intraepithelial lymphocyte count. Immunologic assessment of the intestinal mucosa was made by indirect immunoperoxidase using monoclonal antibodies against CD3, CD4, and CD8. Seven patients with irritable bowel syndrome and two healthy volunteers were selected as a control group for histologic and immunohistochemical comparisons. After 6 weeks the patient group maintained their body weight and increased their tricipital fold. The number of peripheral blood T cells, albumin, transferrin, and the number of CD3+, CD4+, and CD8+ cells in jejunal mucosa as well as the intestinal morphometry remained stable. Oral supplementation contributed to maintaining body weight and may constitute a reasonable adjuvant therapeutic tool against AIDS progression.

Spinal myoclonus: report of four cases

Four cases of spinal myoclonus are described, three males and one female. The mean age was 51 years (28-75 years). The mean time between the onset of the myelopathy and the myoclonic jerks was 4.3 months (1-8 months). The involuntary movements were determined by trauma, Devics disease, tuberculous myelopathy and tumor. Three patients had spastic paraplegia with bilateral myoclonus more evident on the right side. The fourth patient had a flaccid paraplegia with symmetrical jerks. The data suggest that different processes (trauma, demyelinating, infection and tumor) affecting the spinal cord may cause the same type of involuntary movements.

Avaliação colonoscópica em pacientes com espondilite anquilosante

INTRODUCTION Patients with ankylosing spondylitis can have intestinal inflammatory lesions, thus the use of colonoscopy for such patients should be defined. OBJECTIVES To assess the gross intestinal colonoscopic changes and microscopic histopathologic findings of patients with ankylosing spondylitis; to correlate the colonoscopic and histopathologic findings; and to study the relationship of the histopathologic findings with extra-articular manifestations of the disease, HLA-B27, BASFI and BASDAI. METHODS This is a cross-sectional study of 22 patients with ankylosing spondylitis. The patients underwent clinical assessment, BASDAI and BASFI application, blood collection for HLA-B27 measurement, and colonoscopy with biopsy of four intestinal segments (terminal ileum, right and sigmoid colons, and rectum). RESULTS Abnormal colonoscopic results were obtained in 13 (59.1%) patients, the major abnormality being intestinal polyps. The groups of normal and abnormal colonoscopic results (n=9 and n=13, respectively) were homogeneous regarding age, BASFI, BASDAI, and categorical variables, and the P-value showed no significant difference between groups. The histopathological findings revealed abnormal biopsies in 81%, 90.9%, 90.9% and 86.4% for terminal ileum, right colon, sigmoid colon, and rectum, respectively. The histopathologic results showed no statistically significant association with the extra-articular manifestations, BASFI, BASDAI and HLA-B27 positivity. CONCLUSIONS The histological analysis of the four intestinal segments evidenced inflammatory lesions in patients with normal and abnormal colonoscopic results, independently of bowel symptomatology and therapy used in the treatment of the basal disease.